Compounds which modulate release of one or more of the aforementioned inflammatory cytokines can be useful in treating diseases associated with release of these cytokines. For example, WO 98/52558 discloses heteroaryl urea compounds which are indicated to be useful in treating cytokine mediated diseases. WO 99/23091 discloses another class of urea compounds which are useful as anti-inflammatory agents. WO 99/32463 relates to aryl ureas and their use in treating cytokine diseases and proteolytic enzyme mediated disease. WO 00/41698 discloses aryl ureas said to be useful in treating p38 MAP kinase diseases.
Di-substituted aryl and heteroaryl compounds are also disclosed in U.S. Pat. Nos. 6,080,763; 6,319,921; 6,297,381, 6,358,945 and 6,492,393. The compounds in the patents are alleged to possess anti-cytokine activity and are therefore useful in treating diseases associated with inflammation.
U.S. provisional application No. 60/401,921, commonly owned by the assignee of the present application, relates to flourinated di-aryl urea compounds of formula(I):
wherein R1, R2, R3, X and W of formula(I) are defined therein. The compounds inhibit production of cytokines involved in inflammatory processes and are thus useful for treating diseases and pathological conditions involving inflammation. Also disclosed are processes for preparing compounds of the formula (I). The advantage provided by the present invention allows reducing the synthetic sequence to three steps and overcome low yields and exothermic conditions.